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Cholesterol Could be Key to Treating Fetal Alcohol Syndrome

By Duke Medicine News and Communications

Video of the zebrafish and the facility is available in the
following formats: RealMedia,
QuickTime.

DURHAM, N.C. -- Small amounts of alcohol can interfere with
the growth of a fetus, but added cholesterol may help prevent a
wide array of neurological and physical defects from alcohol
exposure, according to a new study in laboratory fish.

Cholesterol is so important to fetal development that
pregnant women who do not have high enough cholesterol levels
are at increased risk of having babies with developmental
problems, even without consuming alcohol. Researchers at Duke
University Medical Center, led by Yin-Xiong Li, MD., Ph.D.,
found that alcohol, even in small amounts, blocks the ability
of cholesterol to orchestrate the complex series of events
involved in regulating cell fates and organ development in the
embryo. Encouragingly, the researchers also found that giving
supplemental cholesterol to zebrafish embryos exposed to
alcohol restored normal development.

Fetal alcohol syndrome is a term to describe an array of
developmental defects affecting the nervous and cardiovascular
systems. The syndrome also can lead to growth retardation,
facial abnormalities and lowered mental functioning. It is
estimated that approximately 100 babies are born in the United
States each day with some degree of alcohol induced birth
defects, at an annual cost of $10 billion to the health care
system.

What alcohol does is interfere with a precisely orchestrated
biochemical signaling pathway that guides fetal development.
Cholesterol is essential for a single pathway that governs the
pattern of tissue development and it is vulnerable to the
effects of alcohol.

"This new insight into the molecular basis of fetal alcohol
syndrome could have far-reaching implications and suggests new
prenatal care that might prevent the developmental defects
caused by alcohol consumed during pregnancy," Li said.

The researchers published the findings in the March 2007
issue of the journal Laboratory Investigation. The research was
supported by the National Institutes of Health and the American
Heart Association.

Li said that the keys to fetal alcohol syndrome's severity
are the amount of alcohol consumed, the duration of the
consumption and the timing of the pregnancy. For example,
alcohol consumed by a mother with a one-month-old fetus could
alter the development of the brain; at four to eight weeks,
facial structures, heart and eyesight could be affected. Two to
three months into fetal development, alcohol consumption could
lead to the growth of extra digits.

"The amount of alcohol consumed is important as well," Li
said. "Even the equivalent of one 12-ounce beer, consumed at
the wrong time, could disrupt the signaling pathway and lead to
a defect."

The team also found that increased amounts of alcohol
exposure by the fetus led to increased severity of the
syndrome.

Li pointed out that the findings could have other
theoretical implications as well. He said giving alcoholics
supplemental cholesterol could help slow down or prevent the
occurrence of alcoholic liver disease, even chronic alcoholic
induced cirrhosis, characterized by replacement of liver tissue
by scar tissue, leading to progressive loss of liver
function.

Also, he said the findings provide further credence to
current practice of ensuring that pregnant women should not
lower their cholesterol too low. A recent study found that
women who took cholesterol-lowering drugs known as statins were
at greater risk of giving birth to babies with developmental
problems.

Other Duke members of the team were Anna Mae Diehl, Hai-Tao
Yang, Marzena Zdanowicz, Yi Qi and Terese Camp. Jason Sicklick
of the Johns Hopkins University School of Medicine also
participated in the study.